Canine infectious respiratory disease complex (CIRDC) is a highly contagious disease that is common in dogs housed in crowded conditions, such as re-homing centers and boarding or training kennels. Many dogs suffer only from a mild cough and recover after a short time. However in some cases, a severe bronchopneumonia can develop.
The pathogenesis of CIRDC is considered to be multifactoral, involving several viruses and bacteria. Infectious agents known to be causative agents of CIRDC include canine respiratory coronavirus (CRCoV) (Erles et al., Virology, 310(2):216-223, 2003), canine influenza virus (CIV) (Crawford et al., Science, 310(5747):482-485, 2005), canine parainfluenzavirus (CPIV) (Binn et al., Exp. Biol. Med., 126:140-145, 1967), canine adenovirus serotype 2 (CAV-2) (Ditchfield et al., Can. Vet. J., 3:238-247, 1962), Mycoplasma cynos (Chalker et al., Microbiology, 150:3491-3497, 2004), and the bacterium Bordetella bronchiseptica (Bemis et al., Lab. Anim. Sci., 29:48-52, 1977).
CRCoV causes a highly contagious respiratory infection which is spread by direct dog-to-dog contact, aerosols of respiratory secretions, and contact with contaminated environments or people. Some dogs have a mild disease with symptoms consisting of cough, sneezing, and nasal discharge. Some dogs have a subclinical infection with no clinical signs, yet they shed virus that can infect other dogs. Some dogs infected with CRCoV progress to pneumonia, particularly if co-infected with other respiratory pathogens.
Regarding CIV, equine influenza virus has been recognized as a major respiratory pathogen in horses since about 1956. Disease symptoms caused by equine influenza virus can be severe, and are often followed by secondary bacterial infections. Two subtypes of equine influenza virus are recognized, namely subtype-1, the prototype being A/Equine/Prague/1/56 (H7N7), and subtype-2, the prototype being A/Equine/Miami/1/63 (H3N8). Presently, the predominant virus subtype is subtype-2, the H3N8 strain. An influenza virus, H3N8 equine influenza virus, is able to infect canines, with fatalities in some cases as high as 36%. One explanation is that an interspecies transfer of the complete or a portion of the equine influenza virus to the dog resulted in a new canine specific influenza virus associated with acute respiratory disease (Crawford et al., 2005).
Disease caused by CPIV is common in the upper respiratory tract. Disease caused by CPIV alone can be mild or subclinical, with signs becoming more severe if concurrent infection with other respiratory pathogens occurs.
CAV-2 causes respiratory disease which, in severe cases, can include pneumonia and bronchopneumonia.
B. bronchiseptica has been reported as being a primary etiological agent in the respiratory disease tracheobronchitis or “kennel cough”. It predisposes dogs to the influence of other respiratory agents, and frequently exists concurrently with them. Kennel cough is typically a condition of the upper airways, and is characterized by nasal discharge and coughing. To date, a number of vaccines are available for treatment of tracheobronchitis caused by Bordetella bronchiseptica, including Nobivac®, Bronchi-Shield®, Bronchicine® CAe, Vanguard® B, Univac 2, Recombitek® KC2, Naramune™-2 and Kennel-Jec™2. However, the majority of existing commercial vaccines require cumbersome intranasal administration as well as the addition of adjuvants, which can result in deleterious side-effects, such as burning and irritation. Viera Scheibner et al., Nexus December 2000 (Vol 8, No 1). Subunit vaccines, such as those involving the use of p68 protein of Bordetella bronchiseptica (pertactin), have been explored but to date have not been included in any commercial canine vaccines, possibly due to insufficient immunogenicity, adverse reactions, and/or formulation stability.
The pathology of CIRDC indicates that it is involved in lung damage and, in some cases, bronchopneumonia, but it is distinct from kennel cough (primary etiological agent: B. bronchiseptica) which mainly involves upper respiratory tract changes. Kennel cough is a milder syndrome than CIRDC, and does not have the wide range of pathology noted in CIRDC. CIRDC is also distinguished by an increased severity and mortality.
CIRDC is rarely fatal, but it delays re-homing of dogs at rescue centers, disrupts schedules in training kennels, and results in considerable treatment costs and welfare concerns. Vaccines are available against some of the infectious agents associated with CIRDC. However, despite the use of these vaccines, CIRDC is still prevalent world-wide, possibly due to the lack of efficacious vaccines against all the infectious agents involved in CIRDC.
Accordingly, there remains a need for an immunogenic composition, capable of being safely administered to a canine, which provides long-acting immunoprotection against the agents that cause CIRDC without deleterious side effects or interference with other antigens in a combination vaccine. The present disclosure fulfils these and other related needs.